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Health

Maybe it's agriculture - soft sweep TRPV6

Gene ExpressionBy Razib KhanFebruary 28, 2008 12:03 AM

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Parallel Selection on TRPV6 in Human Populations (Open Access):

...The selective footprints, however, are significantly differentiated between non-African populations and estimated to be younger than an ancestral population of non-Africans. The possibility of a single selection event occurring in an ancestral population of non-Africans was tested by simulations and rejected. The putatively-selected TRPV6 haplotype contains three candidate sites for functional differences, namely derived non-synonymous substitutions C157R, M378V and M681T. Potential functional differences between the ancestral and derived TRPV6 proteins were investigated by cloning the ancestral and derived forms, transfecting cell lines, and carrying out electrophysiology experiments via patch clamp analysis. No statistically-significant differences in biophysical channel function were found, although one property of the protein, namely Ca^2+ dependent inactivation, may show functionally relevant differences between the ancestral and derived forms. Although the reason for selection on this locus remains elusive, this is the first demonstration of a widespread parallel selection event acting on standing genetic variation in humans, and highlights the utility of between population EHH statistics.

Jump to discussion:

A potential selective force that could result in parallel selection in different populations is agriculture. The independent development of agriculture in several different parts of the world within the past 11,000 years...including the Middle East (11,000 ybp), East Asia (9,000 ybp), the Americas (5,000-4000 ybp), and the New Guinea highlands (9,000-6,000 ybp), fits remarkably well with the demonstrated parallel selection on TRPV6 in the ancestors of Europeans and Asians, and potentially in the Americas and New Guinea as well. It may be that dietary changes related to the switch to agriculture underlie the selective event, or that selection on TRPV6 is related to resistance to a particular disease that became important with the increased population densities associated with agriculture. As a simple test of this hypothesis, we included three hunter-gatherer groups from India in our genotyping of the three tagging SNPs in worldwide populations (Koragas, Mullukurunan, and Mullukurumba...however, all three populations were fixed for the derived, putatively-selected haplotype, suggesting that selection for this haplotype also occurred in the ancestors of these groups. While to the best of our knowledge these populations have always been hunter-gatherers, it is possible that they have reverted from an agricultural to a hunting-gathering lifestyle, as has been documented for other hunting-gathering groups...Genotyping of additional hunter-gatherer groups would therefore be desirable.

I would bet many Old World "hunter-gatherer" populations in close proximity to the Oikumene were driven there, or, gene flow has swamped out any "pure" original signature. In any case, the paper is basically talking about the process whereby extant genetic variation that was always around got selected due to changes in the exogenous pressures. So a switch to a new lifestyle. In contrast, the locus around LCT that's swept in much of Eurasia seems to be derived from a relatively recent mutant.

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